Comparison of onset of neuromuscular blockade with electromyographic and acceleromyographic monitoring: a prospective clinical trial

Abstract Background Reliable devices that quantitatively monitor the level of neuromuscular blockade after neuromuscular blocking agents' administration are crucial. Electromyography and acceleromyography are two monitoring modalities commonly used in clinical practice. The primary outcome of this study is to compare the onset of neuromuscular blockade, defined as a Train-Of-Four Count (TOFC) equal to 0, as measured by an electromyography-based device (TetraGraph) and an acceleromyography-based device (TOFscan). The secondary outcome was to compare intubating conditions when one of these two devices reached a TOFC equal to 0. Methods One hundred adult patients scheduled for elective surgery requiring neuromuscular blockade were enrolled. Prior to induction of anesthesia, TetraGraph electrodes were placed over the forearm of patients' dominant/non-dominant hand based on randomization and TOFscan electrodes placed on the contralateral forearm. Intraoperative neuromuscular blocking agent dose was standardized to 0.5 mg.kg−1 of rocuronium. After baseline values were obtained, objective measurements were recorded every 20 seconds and intubation was performed using video laryngoscopy once either device displayed a TOFC = 0. The anesthesia provider was then surveyed about intubating conditions. Results Baseline TetraGraph train-of-four ratios were higher than those obtained with TOFscan (Median: 1.02 [0.88, 1.20] vs. 1.00 [0.64, 1.01], respectively, p < 0.001). The time to reach a TOFC = 0 was significantly longer when measured with TetraGraph compared to TOFscan (Median: 160 [40, 900] vs. 120 [60, 300] seconds, respectively, p < 0.001). There was no significant difference in intubating conditions when either device was used to determine the timing of endotracheal intubation. Conclusions The onset of neuromuscular blockade was longer when measured with TetraGraph than TOFscan, and a train-of-four count of zero in either device was a useful indicator for adequate intubating conditions. Clinical trial number and registry URL NCT05120999, https://clinicaltrials.gov/ct2/show/NCT05120999.

Uso de infusión continua de bloqueadores neuromusculares en pacientes con COVID-19 en ventilación mecánica invasiva / Use of continuous infusion of neuromuscular blockers in patients with COVID-19 undergoing invasive mechanical ventilation

ANTECEDENTES: El objetivo del presente informe es: Describir el proceso para la elaboración de recomendaciones por el grupo de trabajo designado por el Ministerio de Salud, en adelante denominado grupo de trabajo. Trasladar las Recomendaciones efectuadas por dicho grupo de trabajo en atención al uso de infusión continua de bloqueadores neuromusculares en pacientes con COVID-19 en ventilación mecánica no invasiva, según la pregunta PICO (P: Población, I:Intervención, C:Comparador, O: Outcome o desenlaces) priorizada por el grupo de trabajo. La metodología considerada para arribar a la recomendación fue el Marco de Evidencia a la Decisión/Recomendación (EtD) desarrollado por el Grupo de Trabajo GRADE(1,2). METODOS: Formulación de la pregunta: ¿Debería utilizarse infusión continua de bloqueadores neuromusculares (BNM) versus no hacerlo, en pacientes con COVID-19 en ventilación mecánica invasiva (VMI? ¿Qué medicamento y qué pauta de dosificación debe administrarse? Identificación de la evidencia para la pregunta PICO: Se siguieron las orientaciones establecidas en el documento interno de UNAGESP: Orientaciones para el soporte metodológico otorgado al grupo de trabajo designado por el MINSA. Se describe a continuación los resultados del proceso: Se efectuó la búsqueda de guías de práctica clínica (GPC) que incluyeran recomendaciones respecto al uso de BNM en la población de interés, con fecha de búsqueda 15 de octubre de 2021 en las siguientes plataformas: eCOVID-19 living map of recommendations (eCovid-19 RecMap), Base internacional de Guías GRADE (BIGG) , Guidelines International Network (GIN), COVID-19 Guidelines Dashboard, National Institute for Health and Care Excellence - UK (NICE) y Trip database, identificándose 5 guías de práctica clínica (Ver Anexo 1). En base a criterios como fecha de búsqueda de la evidencia, uso de metodología GRADE para evaluar la certeza de la evidencia, disponibilidad de la tabla Perfil de evidencia o Resumen de hallazgos, disponibilidad de los criterios o Tabla EtD, tipo de recomendación emitida y valoración AGREE II realizada por el equipo de eCovid-19 RecMap, se seleccionó la GPC de Australia titulada "Australian guidelines for the clinical care of people with COVID-19"(5) elaborada por The National COVID-19 Clinical Evidence Taskforce, con fecha de publicación del 15 de octubre de 2021 que utilizó la metodología GRADE para la evaluación de la certeza de la evidencia y el Marco de Evidencia para la decisión (EtD) para esta pregunta PICO, estando disponibles a través de las plataformas magicapp(6) y eCovid RecMap(3). En ésta última plataforma, la evaluación de la calidad metodológica de la GPC mediante la herramienta AGREE II mostró puntajes adecuados en los dominios claves: Alcance y objetivos: 83.3%, Rigor en el desarrollo: 74% e Independencia editorial: 70.8%. La guía no identificó ningún estudio en COVID-19 y la evidencia que informó la recomendación provino de una revisión sistemática y meta-análisis de 5 ensayos clínicos en pacientes con Síndrome de distrés respiratorio agudo (SDRA) por otras causas. Sin embargo, no se identificó la fecha de búsqueda de los estudios ni los métodos realizados para esta revisión sistemática. La recomendación realizada en la GPC de Australia estuvo basada en evidencia con certeza muy baja. Debido a estos resultados, se decidió efectuar una búsqueda de estudios primarios en COVID-19, incorporando parcialmente los términos de búsqueda de la GPC de Australia. La búsqueda se realizó en MEDLINE/ vía Pubmed, plataforma L·OVE de Epistemonikos(7) y en MedRxiv, con fecha 15 de octubre de 2021 (Ver Anexo 1). Los criterios de selección de los estudios fueron: ensayos clínicos aleatorizados, cohortes o casos y control que evaluen la PICO planteada y reportaran al menos uno de los desenlaces de interés. En adición, se efectuó una búsqueda de revisiones sistemáticas de ensayos clínicos, que evaluaran el uso de la infusión continua de BNM en pacientes con SDRA, a fines de obtener evidencia indirecta que complementara los resultados de la búsqueda de estudios primarios en COVID-19. La evaluación de la calidad metodológica de las revisiones sistemáticas se realizó con la herramienta AMSTAR 2(8) y para ensayos clínicos se consideró la evaluación de riesgo de sesgo reportada por la revisión sistemática si esta utilizó la herramienta de Cochrane para ensayos clínicos aleatorios. En caso de estudios observacionales, se empleó la herramienta Risk Of Bias in Non-randomized Studies of Interventions (ROBINS-I)(9). La certeza de la evidencia fue realizada según el enfoque GRADE que toma en cuenta los siguientes criterios: diseño del estudio, riesgo de sesgo, inconsistencia en los resultados, ausencia de evidencia directa, imprecisión, sesgo de publicación, tamaño de efecto, gradiente dosis-respuesta, y efecto de los potenciales factores de confusión residual (los tres últimos aplicables en estudios observacionales)(10,11). Los resultados fueron presentados utilizando la Tablas de Resumen de Hallazgos (SOF, por sus siglas en inglés) construidas a partir del software en línea GRADEpro (https://gradepro.org/)(12). RECOMENDACIÓN: Se sugiere el uso de la infusión continua de bloqueador neuromuscular en pacientes con COVID-19 en ventilación mecánica invasiva con algunas de las siguientes condiciones: Síndrome de distrés respiratorio agudo (SDRA) moderado o grave (PaO2/FiO2 < 150 mmHg) en fase aguda Independientemente del valor de PaO2/FiO2: Asincronía ventilatoria mayor persistente, a pesar de una programación adecuada del ventilador mecánico. Ventilación en posición prona. Necesidad de sedación profunda. Persistencia de presiones plateau altas o PEEP alto. Presencia de barotrauma o riesgo elevado de desarrollarlo. JUSTIFICACIÓN DE LA RECOMENDACIÓN: Se identificó un estudio de cohorte retrospectivo multicéntrico(14) que utilizó la información disponible a través de registros electrónicos de pacientes de 174 centros de investigación en 31 países. El 12% de los centros participantes estaba ubicado en Latinoamérica. El estudio está disponible desde Febrero de 2021 como manuscrito aún no revisado por pares. El estudio incluyó a 2165 pacientes con COVID-19 en VMI, que ingresaron a UCI entre Febrero a Noviembre de 2021, en su mayoría durante la primera ola de la pandemia. El estudio comparó el uso de BNM por 2 o más días, sea uso continuo o intermitente (grupo intervención) versus el uso < 2 días luego del inicio de la VMI (grupo control). En conjunto, la mediana de la duración del BNM fue de 3 días (rango intercuartílico (RIC) 2-6) y en aquellos que usaron el BNM de forma continua, la duración fue de 2 días (RIC 1-5). Sin embargo, el estudio no reportó el BNM utilizado ni la dosis administrada. Asimismo, un 17% de participantes del grupo control llegó a recibir 2 días o más de BNM. La administración de co-intervenciones como pronación, maniobras de reclutamiento y uso de corticoides varió entre los grupos. El estudio realizó emparejamiento por puntaje de propensión en base a características clínicas y sociodemográficas y el análisis multivariado incluyó potenciales factores de confusión como uso de antibióticos, terapia de reemplazo renal continua, ECMO y decúbito prono. Una descripción más detallada del estudio está disponible en el Anexo 2. El estudio reportó un mayor riesgo de mortalidad a los 28 días entre los que habían recibido BNM (HRa: 2.20, IC 95%: 1.67-2.89; 1350 pacientes incluidos en el análisis multivariado). El riesgo de sesgo global fue calificado como Serio, dada la calificación de Serio en los dominios Sesgo debido a confusión, Sesgo en la clasificación de las intervenciones, Sesgo debido a datos perdidos y no información en el dominio Sesgos debido a desviaciones de las intervenciones propuestas, de la herramienta ROBINS-I. La certeza de la evidencia fue calificada como Baja debido a riesgo de sesgo muy serio.

Anafilaxia y anafiláctico / Anaphilactic shock and anaphilaxis

Anaphylaxis is a life-threatening clinical condition that results from the activation of mast cells/basophils, inflammatory pathways, or both. It can be specific (allergic), or non-specific (non-allergic). Most anaphylaxis are mediated by IgE, but there are also some mediated by IgM and complement activation. Incidence is about 1:10,000 anesthesia. Recent studies show that the drugs or substances mostly implicated in producing perioperative anaphylaxis are: neuromuscular blockers (60.6%), antibiotics (18.2%), patent blue dye (5.4%) and latex (5.2%). However, all drugs and substances used during anesthesia and surgery, perhaps with the sole exception of inhalation agents and crystalloids, have been reported as potentially causes of anaphylaxis. The clinical presentation is multisystemic, producing signs and symptoms mainly on skin, respiratory, cardiovascular, gastrointestinal and central nervous systems. In its advanced phase, it may evolve to anaphylactic shock, causing tissue hypoperfusion and leading to altered cell integrity and multiple organ failure, associated with high mortality. Diagnosis is based on clinical presentation (history and clinical manifestations), biological evidence (serum tryptase levels, serum histamine levels and search for specific IgE) and allergological evidence (skin tests, provocation test, mediator release tests and tests of activation of basophils). Treatment include 3 stages: general measures, first-line or primary treatment and second-line or secondary treatment. General measures consist of: Trendelenburg position, invasive monitoring (according to the severity of the clinical presentation), 100% oxygen administration, discontinuation of drugs and/or suspected agents and asking for help. The primary treatment is epinephrine in doses proportional to the clinical manifestations, airway support, 100% oxygen and aggressive resuscitation with intravenous fluids. Secondary treatment includesadministration of bronchialodilators, corticosteroids, and antihistamines.

Una anafilaxia es una condición clínica potencialmente mortal que resulta de la activación específica (alérgica), o no específica (no alérgica) de mastocitos/ basófilos, vías inflamatorias o ambos. La mayoría de las anafilaxias son mediadas por IgE, pero también las hay por IgM y activación del complemento. Su incidencia es de 1:10.000 anestesias. En los últimos estudios, los fármacos o sustancias más implicadas en producir anafilaxia perioperatoria son los bloqueadores neuromusculares (60,6%), los antibióticos (18,2%), las tinturas azules (5,4%) y el látex (5,2%), sin embargo, todas las drogas y sustancias usadas durante la anestesia y la cirugía, tal vez con la única excepción de los agentes inhalatorios y los cristaloides, han sido reportadas como potencialmente causantes de anafilaxia. El cuadro clínico es multisistémico, originando signos y síntomas centrados en la piel y los sistemas respiratorio, cardiovascular, gastrointestinal y nervioso central. En su fase avanzada puede evolucionar a anafiláctico, causando hipoperfusión tisular y llevando a alteración en la integridad celular y falla de múltiples órganos, con alta mortalidad asociada. El diagnóstico se basa en evidencias clínicas (historia y manifestaciones clínicas), evidencias biológicas (niveles de triptasa sérica, de histamina sérica y búsqueda de IgE específicas) y evidencias alergológicas (pruebas cutáneas, test de provocación, pruebas de liberación de mediadores y pruebas de activación de basófilos. El tratamiento incluye 3 etapas: medidas generales, tratamiento de primera línea o primario y tratamiento de segunda línea o secundario. Las medidas generales consisten en poner al paciente en posición de Trendelemburg, iniciar monitorización invasiva según la intensidad del cuadro clínico, administración de oxígeno al 100%, discontinuación de drogas y/o agentes posiblemente incriminados y pedir ayuda. El tratamiento primario es la adrenalina, en dosis proporcionales a las manifestaciones clínicas, el soporte de la vía aérea manteniendo el oxígeno ql 100% y la reanimación agresiva con fluidos endovenosos. El tratamiento secundario incluye la administración de broncodilatadores, corticoesteroides y antihistamínicos.

Enfermería de urgencias en la intubación de secuencia rápida a pacientes COVID-19 / Cuidados de enfermagem de emergência para intubação de sequência rápida em pacientes com COVID-19 / Emergency Nursing Care for Rapid Sequence Intubation in COVID-19 Patients

Introducción: La inducción de secuencia rápida modificada es la sugerida para la intubación orotraqueal a pacientes COVID-19 que presentan distrés respiratorio en urgencias. El objetivo de esta revisión es plantear el proceso de atención de enfermería durante las fases de planificación, preparación, pretratamiento y sedación con parálisis neuromuscular. Materiales y Métodos: artículo de reflexión acerca de elementos conceptuales en la valoración, diagnóstico, planeación, ejecución y evaluación del cuidado de enfermería, a partir de la revisión de literatura de consensos y protocolos nacionales e internacionales y publicaciones de cuidado de enfermería a pacientes COVID-19. Resultados: los medicamentos recomendados por la literatura en la inducción de secuencia rápida a pacientes COVID-19 son: en la fase de pretratamiento, las benzodiacepinas necesarias para disminuir la ansiedad del paciente, la lidocaína que controla el reflejo de la tos y el fentanilo que contribuye con la analgesia; en la fase de sedación inductores como etomidato y ketamina están indicados en pacientes con inestabilidad hemodinámica y propofol en pacientes estables; en la fase de parálisis neuromuscular el rocuronio es el recomendado como primera opción antes que la succinilcolina y los vasopresores tipo norepinefrina, epinefrina, vasopresina y/o dopamina, son necesarios en todas las fases para el manejo de la inestabilidad hemodinámica. Conclusiones: aplicar el proceso de atención de enfermería durante las fases de inducción de secuencia rápida contribuye con la organización de los medicamentos requeridos para la intubación orotraqueal, lo cual, disminuye la ansiedad del paciente y el riesgo de contaminación del personal de salud.

Introduction: Modified rapid sequence induction is suggested for orotracheal intubation in COVID-19 patients with respiratory distress in the emergency department. The objective of this review is to discuss nursing care during the phases of planning, preparation, pretreatment and sedation with neuromuscular paralysis. Materials and Methods: A reflection article was written on conceptual elements in nursing care assessment, diagnosis, planning, implementation and evaluation based on the literature review of national and international standards and protocols, and publications on nursing care in COVID-19 patients. Results: Drugs recommended by rapid sequence intubation in COVID-19 patients are benzodiazepine for reducing patient's anxiety, lidocaine for cough control and fentanyl for analgesia in the pretreatment phase; inducers such as etomidate and ketamine are suggested in hemodynamic unstable patients and propofol in stable patients in the sedation phase; rocuronium is recommended as the first-choice neuromuscular blocking agent before vasopressors such as succinylcholine and norepinephrine, epinephrine, vasopressin and/or dopamine which are needed in all phases for managing hemodynamic instability. Conclusions: Applying a nursing care plan during rapid sequence induction phases contributes to a more organized medication regimen required for orotracheal intubation, which reduces patient's anxiety and the risk of contamination for healthcare personnel.

Introdução: A indução de sequência rápida modificada é sugerida para intubação orotraqueal em pacientes com COVID-19 com problemas respiratórios no departamento de emergência. O objetivo desta revisão é discutir os cuidados de enfermagem durante as fases de planejamento, preparação, pré-tratamento e sedação com paralisia neuromuscular. Materiais e métodos: Um artigo de reflexão foi elaborado sobre elementos conceituais na avaliação, diagnóstico, planejamento, implementação e avaliação da cuidados de enfermagem com base na revisão da literatura de normas e protocolos nacionais e internacionais, e publicações sobre cuidados de enfermagem em pacientes com COVID-19. Resultados: As drogas recomendadas pela intubação de sequência rápida em pacientes com COVID-19 são benzodiazepinas para reduzir a ansiedade do paciente, lidocaína para controle da tosse e fentanil para analgesia na fase de pré-tratamento; indutores como etomidato e cetamina são sugeridos em pacientes com instabilidade hemodinâmica e propofol em pacientes estáveis na fase de sedação; o rocurônio é recomendado como o bloqueador neuromuscular de primeira opção frente a vasopressores como succinilcolina e norepinefrina, epinefrina, vasopressina e/ou dopamina, que são necessários em todas as fases para o manejo da instabilidade hemodinâmica. Conclusões: A aplicação de um plano de cuidados de enfermagem durante as fases de indução de sequência rápida contribui para a organização dos medicamentos necessários para a intubação orotraqueal, o que reduz a ansiedade do paciente e o risco de contaminação para o pessoal de saúde.

Informe diário de evidências COVID-19: busca referente aos dias 25, 26 e 27 de julho de 2020 / COVID-19 daily evidence report: search for July 25, 26 and 27, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos e 8 protocolos.

Protocolo nacional de sedación y analgesia en UCI COVID-19 / National protocol for sedation and analgesia in ICU COVID-19

El presente documento tiene la finalidad de guiar a los médicos que manejan la unidad de cuidados intensivos en los Hospitales Temporales Nacionales que atienden pacientes con COVID-19 en cuanto a la aplicación de sedación y analgesia. Una adecuada sedoanalgesia y el uso de bloqueantes neuromusculares permitirán asegurar la provisión de ventilación mecánica protectora durante la inducción para intubación y el mantenimiento, limitar el desarrollo de lesión pulmonar por ventilación espontánea con una alta demanda respiratoria Incluye un Flujograma de Algoritmos de análogo sedación en el paciente crítico bajo ventilación mecánica

Events associated with the occurrence of intracranial hypertension in pediatric patients with severe cranioencephalic trauma and monitoring of intracranial pressure / Eventos associados à ocorrência de hipertensão intracraniana em pacientes pediátricos com traumatismo cranioencefálico grave e monitoração da pressão intracraniana

ABSTRACT Objective: To determine the events associated with the occurrence of intracranial hypertension (ICH) in pediatric patients with severe cranioencephalic trauma. Methods: This was a prospective cohort study of patients 18 years old and younger with cranioencephalic trauma, scores below nine on the Glasgow Coma Scale, and intracranial pressure monitoring. They were admitted between September, 2005 and March, 2014 into a Pediatric Intensive Care Unit. ICH was defined as an episode of intracranial pressure above 20 mmHg for more than five minutes that needed treatment. Results: A total of 198 children and adolescents were included in the study, of which 70.2% were males and there was a median age of nine years old. ICH occurred in 135 (68.2%) patients and maximum intracranial pressure was 36.3 mmHg, with a median of 34 mmHg. A total of 133 (97.8%) patients with ICH received sedation and analgesia for treatment of the condition, 108 (79.4%) received neuromuscular blockers, 7 (5.2%) had cerebrospinal fluid drainage, 105 (77.2%) received mannitol, 96 (70.6%) received hyperventilation, 64 (47.1%) received 3% saline solution, 20 (14.7%) received barbiturates, and 43 (31.9%) underwent a decompressive craniectomy. The events associated with the occurrence of ICH were tomographic findings at the time of admission of diffuse or hemispheric swelling (edema plus engorgement). The odds ratio for ICH in patients with Marshall III (diffuse swelling) tomography was 14 (95%CI 2.8-113; p<0.003), and for those with Marshall IV (hemispherical swelling) was 24.9 (95%CI 2.4-676, p<0.018). Mortality was 22.2%. Conclusions: Pediatric patients with severe cranioencephalic trauma and tomographic alterations of Marshall III and IV presented a high chance of developing ICH.

RESUMO Objetivo: Determinar eventos associados à ocorrência de hipertensão intracraniana (HIC) em pacientes pediátricos com traumatismo cranioencefálico grave. Métodos: Trata-se de coorte prospectiva de pacientes de até 18 anos, com traumatismo cranioencefálico, pontuação abaixo de nove na Escala de Coma de Glasgow e monitoração da pressão intracraniana, admitidos entre setembro de 2005 e março de 2014 em unidade de terapia intensiva pediátrica. A HIC foi definida como episódio de pressão intracraniana acima de 20 mmHg por mais de cinco minutos e com necessidade de tratamento. Resultados: Incluídas 198 crianças e adolescentes, 70,2% masculinos, mediana de idade de nove anos. A HIC ocorreu em 135 (68,2%) pacientes; valor máximo de pressão intracraniana de 36,3; mediana 34 mmHg. Receberam sedação e analgesia para tratamento da HIC 133 (97,8%) pacientes, 108 (79,4%) receberam bloqueadores neuromusculares, 7 (5,2%) drenagem de líquor, 105 (77,2%) manitol, 96 (70,6%) hiperventilação, 64 (47,1%) solução salina a 3%, 20 (14,7%) barbitúricos e 43 (31,9%) foram submetidos à craniectomia descompressiva. Os eventos associados à ocorrência de HIC foram os achados tomográficos à admissão de swelling (edema mais ingurgitamento) difuso ou hemisférico. A razão de chance para que pacientes com classificação tomográfica Marshall III (swelling difuso) apresentassem HIC foi 14 (IC95% 2,8-113; p<0,003) e para aqueles com Marshall IV (hemisférico) foi 24,9 (IC95% 2,4-676; p<0,018). A mortalidade foi de 22,2%. Conclusões: Pacientes pediátricos com traumatismo cranioencefálico grave e alterações tomográficas tipo Marshall III e IV apresentaram grande chance de desenvolver HIC.

Is 1 mg/kg of sugammadex sufficient to reverse moderate neuromuscular block? A randomized clinical trial / ¿Es suficiente 1mg/kg de sugammadex para revertir el bloqueo neuromuscular moderado? Ensayo clínico aleatorizado

Abstract Background: Sugammadex has made it possible to reverse any type of rocuronium-induced block quickly and safely. The most frequent neuromuscular blockade is the moderate one where doses smaller than those recommended by the industry could get a full reversal. Objective: We aimed to evaluate the effectiveness of half the industry recommended dose of sugammadex to reverse a moderate neuromuscular block. Methods: Unicenter phase IV clinical trial that included 34 patients undergoing laparoscopic cholecystectomy. Intravenous general anesthesia was induced, with acceleromyographic monitoring of the neuromuscular block. After the intervention, the block was reversed with all or half the dose of sugammadex recommended for moderate blocks, using a blinded syringe. Results: Patient characteristics of the 2 groups were similar. Mean time to recovery was 3.6± 1.7minutes for the study group and 3.1 ± 1.7minutes for the control group (P=0.42). Reversal of the block was complete with a single dose of sugammadex in all patients. There was an important linear correlation between depth of block and time to recovery. Conclusion: Intraoperative monitoring is essential to allow us to individualize the dose of the neuromuscular blocking agent. To reverse a moderate block under neuromuscular monitoring, a dose of 1 mg/kg is sufficient in most cases and is equally safe and effective.

Resumen Introducción: El sugammadex permite revertir cualquier tipo de bloqueo inducido por rocuronio de forma rápida y segura. El bloqueo neuromuscular más frecuente es el moderado, en el cual dosis inferiores a las recomendadas por la industria podrían revertirlo completamente. Objetivo: Evaluar la efectividad de la mitad de la dosis de sugammadex recomendada por la industria para revertir un bloqueo neuromuscular moderado. Métodos: Ensayo clínico de fase IV en un unico centro que incluyó a 34 pacientes intervenidos de colecistectomía laparoscópica. Se realizó anestesia general intravenosa con monitoreo aceleromiográfico del bloqueo neuromuscular. Tras la intervención, el bloqueo se revirtió con la totalidad o con la mitad de la dosis de sugammadex recomendada para bloqueos moderados, utilizando una jeringa ciega. Resultados: Las características de los pacientes de los dos grupos fueron similares. La media de tiempo de recuperación fue de 3,6 ± 1,7 minutos para el grupo de estudio y de 3,1 ± 1,7 minutos para el grupo de control (p = 0,42). La reversión del bloqueo se completó con una dosis única de sugammadex en todos los pacientes. Hubo una correlación lineal importante entre la profundidad del bloqueo y el tiempo de recuperación. Conclusión: El monitoreo transquirúrgico es esencial para individualizar la dosis del agente de bloqueo neuromuscular. Para revertir un bloqueo moderado bajo monitoreo neuromuscular, una dosis de 1mg/kg es suficiente e igualmente segura y efectiva.

Effect of intraoperative neuromonitoring on efficacy and safety using sugammadex in thyroid surgery: randomized clinical trial

PURPOSE: The use of nondepolarizing neuromuscular blocking agents (NMBAs) may affect intraoperative neuromonitoring (IONM) during anesthesia used during thyroid and parathyroid surgery. METHODS: The use of sugammadex was evaluated in a prospective clinical study during thyroid surgery. Between July 2018 and January 2019, 129 patients were prospectively randomized to either the sugammadex group (group B) or the control group (group A). Group A patients underwent standardized IONM during thyroidectomy, while group B patients used an NMBA-reversal protocol comprised of rocuronium (0.6 mg/kg) in anesthesia induction and sugammadex (2 mg/kg) after first vagal stimulation (V0). A peripheral nerve stimulator was used to monitor the neuromuscular transmission. RESULTS: In our clinical study, it took 26.07 ± 3.26 and 50.0 ± 8.46 minutes to reach 100% recovery of laryngeal electromyography at injection of the sugammadex group (2 mg/kg) and the control group, respectively (P 0.9 within 4 minutes after administering 2 mg/kg of sugammadex at the beginning of resection. Surgery time was significantly shorter in group B than in group A (P < 0.001). Transient recurrent laryngeal nerve (RLN) paralysis was detected in 4 patients from group A and in 3 patients from group B (P = 0.681). There was no permanent RLN paralysis in the 2 groups. CONCLUSION: Our clinical study showed that sugammadex effectively and rapidly improved the inhibition of neuromuscular function induced by rocuronium. The implementation of the nondepolarizing neuromuscular block recovery protocol may lead to tracheal intubation as well as favorable conditions for IONM in thyroid surgery.

Current use of neuromuscular blocking agents and antagonists in Korea: a 2018 survey

BACKGROUND: Neuromuscular blocking agents (NMBAs) and neuromuscular monitoring in anesthetic management are integral for endotracheal intubation, better visualization of the surgical field, and prevention of residual neuromuscular blockade and pulmonary complications. Sugammadex is a drug that reduces risk of residual neuromuscular blockade, with more rapid recovery compared to anticholinesterase. The purpose of this study was to investigate current usage status of NMBAs and antagonist with neuromuscular monitoring, among anesthesiologists in Korea.METHODS: Anesthesiologists working in Korea were invited to participate in an online survey via email January 2–February 28, 2018. The questionnaire consisted of 45 items, including preferred NMBAs, antagonists, neuromuscular monitoring, and complications related to the use sugammadex. A total of 174 responses were analyzed.RESULTS: Rocuronium was a commonly used NMBA for endotracheal intubation (98%) of hospitals, and maintenance of anesthesia (83.3%) in of hospitals. Sugammadex, pyridostigmine, and neostigmine were used in 89.1%, 87.9%, and 45.4% of hospitals. Neuromuscular monitoring was employed in 79.3% of hospitals; however only 39.7% of hospitals used neuromuscular monitoring before antagonist administration. Usual dosage range of sugammadex was 2.1–4 mg/kg in 35.1% of hospitals, within 2 mg/kg in 34.5% of hospitals, and 1 vial regardless of body weight in 22.4% of hospitals. Sugammadex-related complications were encountered by 14.9% of respondents.CONCLUSIONS: This survey indicates several minor problems associated with the use of antagonists and neuromuscular monitoring. However, most anesthesiologists appear to have appropriate information regarding the usage of NMBAs and sugammadex.

Anaphylactic shock after sugammadex administration, induced by formation of a sugammadex-rocuronium complex: a case report / 대한마취과학회지

BACKGROUND: Sugammadex is a reversal agent for non-depolarizing neuromuscular blockers and widely used worldwide on account of its rapid and effective reversal from neuromuscular blockade, despite its advantages, multiple cases of sugammadex-induced anaphylactic shock have been reported. CASE: A 42-year-old man developed anaphylactic shock in the postanesthesia care unit. Initially, sugammadex was suspected as the causative agent, but an intradermal skin test revealed negative results. A further skin test was performed with sugammadex-rocuronium complex that yielded positive results. CONCLUSIONS: Anesthesiologists and healthcare providers should be aware of the possibility of anaphylaxis from the sugammadex-rocuronium complex, as well as from sugammadex or rocuronium alone.

Effects of dexamethasone and hydrocortisone on rocuronium-induced neuromuscular blockade and reversal by sugammadex in phrenic nerve-hemidiaphragm rat model / 대한마취과학회지

BACKGROUND: The facilitator effects of steroids on neuromuscular transmission may cause resistance to neuromuscular blocking agents. Additionally, steroids may hinder sugammadex reversal of neuromuscular blockade, but these findings remain controversial. Therefore, we explored the effect of dexamethasone and hydrocortisone on rocuronium-induced neuromuscular blockade and their inhibitory effect on sugammadex. METHODS: We explored the effects of steroids, dexamethasone and hydrocortisone, in vitro using a phrenic nerve-hemidiaphragm rat model. In the first phase, an effective dose of rocuronium was calculated, and in the second phase, following sugammadex administration, the recovery of the train-of-four (TOF) ratio and T1 was evaluated for 30 minutes, and the recovery index was calculated in dexamethasone 0, 0.5, 5, and 50 μg/ml, or hydrocortisone 0, 1, 10, or 100 μg/ml. RESULTS: No significant effect of steroids on the effective dose of rocuronium was observed. The TOF ratios at 30 minutes after sugammadex administration were decreased significantly only at high experimental concentrations of steroids: dexamethasone 50 μg/ml and hydrocortisone 100 μg/ml (P < 0.001 and P = 0.042, respectively). There were no statistical significances in other concentrations. No differences were observed in T1. Recovery index was significantly different only in 100 μg/ml of hydrocortisone (P = 0.03). CONCLUSIONS: Acute exposure to steroids did not resist the neuromuscular blockade caused by rocuronium. And inhibition of sugammadex reversal on rocuronium-induced neuromuscular blockade is unlikely at typical clinical doses of dexamethasone and also hydrocortisone. Conclusively, we can expect proper effects of rocuronium and sugammadex when dexamethasone or hydrocortisone is used during general anesthesia.

Bloqueadores neuromusculares en infusión continua en anestesia general endovenosa total / Neuromuscular blocking drugs in continuous infusion in total intravenous general anesthesia

Introducción: La administración de agentes anestésicos de forma endovenosa dio inicio a una nueva modalidad que implicó la administración de anestésicos en forma de infusiones continuas. Objetivo: Actualizar la información sobre la función de los bloqueadores neuromusculares cuando se administran en infusión continua en anestesia general endovenosa total. Desarrollo: Los bloqueadores neuromusculares se pueden administrar en infusión continua para mantener una concentración plasmática estable y lograr una adecuada relajación del paciente durante el procedimiento quirúrgico, así como una recuperación más rápida y segura de forma espontánea, basándose en el inicio de acción del fármaco utilizado, pero fundamentalmente del alcance de su efecto máximo. A pesar de ello es importante administrar una dosis de carga inicial que deben oscilar entre 2 y 3 DE 95 (dosis efectiva para disminuir la respuesta al estímulo en 95 por ciento de su valor inicial) y continuar con la administración en infusión continúa como parte del mantenimiento de la anestesia. Conclusiones: Independientemente de los diferentes criterios entre autores, la mayoría coinciden que las infusiones continuas logran mantener mayor estabilidad en sangre y por ende, menor dosis de bloqueadores neuromuscular, menores tiempos reales de reversión y menos efectos adversos(AU)

Introduction: The administration of anesthetic agents intravenously started a new modality that involved the administration of anesthetics in the form of continuous infusions. Objective: To update the information on the function of neuromuscular blocking drugs when administered in continuous infusion in total intravenous general anesthesia. Development: Neuromuscular blocking drugs can be administered in continuous infusion to maintain a stable plasma concentration and achieve adequate relaxation of the patient during the surgical procedure, as well as a faster and safer spontaneous recovery, based on the action onset of the drug used, but fundamentally on its maximum effect. Despite this, it is important to administer an initial loading dose that must range from 2 to 3 DE 95 (effective dose to decrease the response to the stimulus in 95 percent of its initial value) and continue with the administration in continuous infusion as part of the maintenance of anesthesia. Conclusions: Regardless the different criteria among authors, most agree that continuous infusions are effective in maintaining greater blood stability and, therefore, lower doses of neuromuscular blocking drugs, shorter real reversal times and fewer adverse effects(AU)

Sugammadex by ideal body weight versus 20% and 40% corrected weight in bariatric surgery - double-blind randomized clinical trial / Uso de sugamadex pelo peso corporal ideal versus corrigido em 20% e 40% em cirurgia bariátrica - ensaio clínico randômico e duplo-cego

Abstract Background and objectives: The weight parameters for use of sugammadex in morbidly obese patients still need to be defined. Methods: A prospective clinical trial was conducted with sixty participants with body mass index ≥ 40 kg.m-2 during bariatric surgery, randomized into three groups: ideal weight (IW), 20% corrected body weight (CW20) and 40% corrected body weight (CW40). All patients received total intravenous anesthesia. Rocuronium was administered at dose of 0.6 mg.kg-1 of Ideal weight for tracheal intubation, followed by infusion of 0.3-0.6 mg.kg-1.h-1. Train of four (TOF) was used to monitor depth of blockade. After spontaneous recovery TOF-count 2 at the end of surgery, 2 mg.kg-1 of sugammadex was administered. Primary outcome was neuromuscular blockade reversal time to TOF ≥ 0.9. Secondary outcome was the occurrence of postoperative residual curarization in post-anesthesia recovery room, searching the patient's ability to pass from the surgical bed to the transport, adequacy of oxygenation, respiratory pattern, ability to swallow saliva and clarity of vision. Results: Groups were homogenous in gender, age, total body weight, ideal body weight, body mass index, type and time of surgery. The reversal times (s) were (mean ± standard deviation) 225.2 ± 81.2, 173.9 ± 86.8 and 174.1 ± 74.9 respectively, in the IW, CW20 and CW40 groups (p = 0.087). Conclusions: No differences were observed between groups with neuromuscular blockade reversal time and frequency of postoperative residual curarization. We concluded that ideal body weight can be used to calculate sugammadex dose to reverse moderate neuromuscular blockade in morbidly obese patients.

Resumo Justificativa e objetivos: Os parâmetros de peso para o uso de sugamadex em pacientes com obesidade mórbida ainda precisam ser definidos. Métodos: Um ensaio clínico prospectivo foi feito com 60 participantes com índice de massa corporal ≥ 40 kg.m-2, submetidos a cirurgia bariátrica, randomizados em três grupos: peso ideal (PI), peso corrigido em 20% (PC20) e peso corrigido em 40% (PC40). Todos os pacientes receberam anestesia intravenosa total. Rocurônio foi administrado em dose de 0,6 mg.kg-1 para intubação traqueal pelo peso ideal, seguido de infusão (0,3 a 0,6 mg.kg-1.h-1). A sequência de quatro estímulos (TOF) foi usada para monitorar a profundidade do bloqueio. Após recuperação espontânea da segunda resposta do TOF no fim da cirurgia, 2 mg.kg-1 de sugamadex foi administrado. O desfecho primário foi o tempo de reversão do bloqueio neuromuscular até obter TOF ≥ 0,9. O desfecho secundário foi a ocorrência de curarização residual pós-operatória na sala de recuperação pós-anestésica, avaliaram-se a capacidade do paciente de passar do leito cirúrgico para o de transporte, a adequação da oxigenação, o padrão respiratório, a habilidade para deglutir saliva e a clareza de visão. Resultados: Os grupos foram homogêneos quanto a gênero, idade, peso corporal total, peso corporal ideal, índice de massa corporal, tipo e tempo de cirurgia. Os tempos de reversão (segundos) foram (média ± desvio-padrão) 225,2 ± 81,2, 173,9 ± 86,8 e 174,1 ± 74,9, respectivamente, nos grupos PI, PC20 e PC40 (p = 0,087). Conclusões: Não foram observadas diferenças entre os grupos quanto ao tempo de reversão do bloqueio neuromuscular e frequência de curarização residual pós-operatória. Concluímos que o peso corporal ideal pode ser usado para calcular a dose de sugamadex para reverter o bloqueio neuromuscular moderado em pacientes com obesidade mórbida.

Interacción farmacológica de los bloqueadores neuromusculares con fármacos de uso anestesiológico / Neuromuscular-blocking drugs interaction with drugs used in anesthesiology

Introducción: Se entiende por interacción farmacológica la capacidad que tiene un fármaco de alterar los efectos farmacológicos de otro que se administre simultáneamente. Objetivo: Realizar una revisión actualizada de la interacción farmacológica de los bloqueadores neuromusculares con fármacos de uso frecuente en el ámbito anestesiológico. Desarrollo: Los mecanismos de interacción medicamentosa son variados y se complican cuando se trata de modificaciones sobre las propiedades farmacocinéticas y farmacodinámicas de cada medicamento. Los bloqueadores neuromusculares (BNM) son fármacos que se utilizan para relajar la musculatura estriada y garantizar la intubación traqueal, la ventilación y producir un plano quirúrgico suficiente para que el cirujano pueda realizar de forma adecuada el procedimiento quirúrgico. Muchos medicamentos interactúan con los BNM y con frecuencia potencian el efecto relajante muscular. Esto resulta de importancia clínica en el caso de antibióticos, anestésicos inhalatorios, litio y ciclosporina. Conclusiones: El anestesiólogo moderno debe tener suficientes conocimientos teóricos sobre las diferentes interacciones medicamentosas que se pueden presentar en el perioperatorio. Los bloqueadores neuromusculares pueden interactuar con fármacos de uso común por los pacientes o por el anestesiólogo, por lo que es necesario el diagnóstico precoz y el tratamiento adecuado para evitar las complicaciones(AU)

Introduction: Drug interaction is understood as the ability of a drug for altering the pharmacological effects of another simultaneously administered. Objective: To carry out an updated review about the drug interaction of neuromuscular-blocking drugs with others frequently used in the anesthesiological field. Findings: The mechanisms of drug interaction are varied and are complicated in cases of modifications on the pharmacokinetical and pharmacodynamical properties of each medicine. Neuromuscular-blocking drugs (NMBs) are used to relax the striated musculature and to ensure tracheal intubation, ventilation. They produce a sufficient surgical plane in order for the surgeon to perform the surgical procedure properly. Many medications interact with NMBs and often potentiate the muscle relaxant effect. This is of clinical importance in the case of antibiotics, inhalational anesthetics, lithium and cyclosporine. Conclusions: Modern anesthesiologists must have sufficient theoretical knowledge about different drug interactions that may occur during the perioperative period. Neuromuscular-blocking drugs can interact with others commonly used by patients or by the anesthesiologists, a reason why early diagnosis and appropriate treatment are necessary to avoid complications(AU)

Effect of levetiracetam on rocuronium duration in patients undergoing cerebrovascular surgery

BACKGROUND: It has long been held that antiepileptics reduce the duration of action, and increase the requirement for, neuromuscular blocking agents. However, levetiracetam, a relatively novel antiepileptic agent, possesses different pharmacokinetic properties to other, conventional antiepileptics, such that its effect on neuromuscular blocking agents might also differ. The purpose of this retrospective study is to investigate the effect of levetiracetam on the clinical duration of rocuronium. METHODS: In this study, the duration of neuromuscular blockade induced by rocuronium was compared between control and levetiracetam-receiving groups. The data were retrieved from one of our previous studies. RESULTS: The control and levetiracetam groups comprised 16 and 13 patients, respectively, all of whom underwent cerebrovascular surgery. Subjects received supplementary rocuronium (0.15 mg/kg) whenever the train-of-four count reached 2 during surgery. The interval between supplementary rocuronium (0.15 mg/kg) injections was significantly longer in the levetiracetam vs. control group (50 and 39 minutes, respectively; P = 0.036). CONCLUSIONS: The present results challenge the convention that antiepileptics decrease the duration of action of neuromuscular blockers, thereby alerting clinicians to the possibility of prolonged neuromuscular blockade in patients taking levetiracetam. Anesthetic management should encompass careful neuromuscular monitoring in such patients.

Response to neuromuscular blockade with rocuronium during general anesthesia in a patient with dermatomyositis: A case report

Dermatomyositis is an idiopathic inflammatory myopathy characterized by skin changes and muscle weakness. Depending on the involvement of various muscles, dermatomyositis can cause aspiration pneumonia, ventilatory impairment, and heart failure. Several reports have documented normal or prolonged neuromuscular blockade following administration of different non-depolarizing neuromuscular blockers in patients with dermatomyositis. We observed delayed onset of blockade and prolonged recovery following administration of 0.6 mg/kg rocuronium in a patient with dermatomyositis. However, when the train-of-four ratio reached 0.3, the patient was administered pyridostigmine and glycopyrrolate, which led to normal response to reversal of rocuronium. The patient was extubated without respiratory complications. The outcomes of this case indicate that response to the usual dosage of muscle relaxants in patients with dermatomyositis might be different from that in patients without this condition. Anesthesiologists should pay attention to preoperative cardiorespiratory evaluation and intraoperative neuromuscular monitoring.

Intradermal skin tests for rocuronium and cisatracurium in patients with a history of allergy: a retrospective study / 대한마취과학회지

BACKGROUND: Neuromuscular blocking agents (NMBAs) are a leading cause of perioperative anaphylaxis. However, the performance of systematic screening skin tests to detect reactions for NMBAs prior to general anesthesia is not recommended. We retrospectively examined intradermal tests (IDTs) for rocuronium and cisatracurium in patients with a history of allergy. METHODS: We reviewed the records of patients who underwent IDTs for NMBAs between January 1 and December 31, 2016. We analyzed the patients’ allergy histories and skin test results for NMBAs. RESULTS: The overall prevalence of positive IDTs was 5.8% (26/451), and there was no significant difference in prevalence among allergy types (P = 0.655). In logistic regression analysis, there was no allergy history that had a significant effect on positive IDT for NMBAs. CONCLUSIONS: We found no association between allergy history and positive skin test for NMBAs. Therefore, a systematic screening test for NMBAs or other anesthetic agents before anesthesia is not considered necessary even in patients with an allergy history.

Updated review of resistance to neuromuscular blocking agents

Since neuromuscular blocking agents (NMBAs) were introduced to the surgical field, they have become almost mandatory for the induction and maintenance of anesthesia. However, resistance to NMBAs can develop in certain pathological states, such as central nerve injury, burns, and critical illnesses. During such pathological processes, quantitative and qualitative changes occur in the physiology of acetylcholine and the acetylcholine receptor (AChR) at the neuromuscular junction. Up-regulation of AChR leads to changes in the pharmacokinetics and pharmacodynamics of NMBA. As NMBA resistance may result in problems during anesthesia, it is of utmost importance to understand the mechanisms of NMBA resistance and their associations with pathological status to maintain adequate neuromuscular relaxation. This review presents the current knowledge of pharmacokinetic and pharmacodynamic changes and pathological status associated with NMBA resistance.